Delayed cerebral ischaemia: the pathological substrate.

Ischaemic complications both at the level of the cortex and the hypothalamus are well recognised after an aneurysmal subarachnoid haemorrhage. We have studied histological changes in the cortex (53 patients) and hypothalamus (48 patients) in patients who died after an aneurysmal subarachnoid haemorrhage. Cortical ischaemic lesions were demonstrated in 41 of the 53 patients studied. These changes were more common in patients who had impaired control of systemic blood pressure (p = 0.0004) and in patients who died gradually (p = 0.0003). Hypothalamic lesions were found in 24 of 48 patients studied; 23 of these patients had widespread associated changes in the cerebral cortex. Patients with moderate/severe cortical changes tended to have hypothalamic lesions and it was uncommon for patients with no cortical lesions to have changes in the hypothalamus (p = 0.0007). We believe that these histological changes are due to diffuse microangiopathy which develops slowly after a subarachnoid haemorrhage and affects the cortex and hypothalamus. Because the cortical lesions are widespread we postulate that they may be implicated in the aetiology of the well described psychosocial or cognitive problems in patients who survive a subarachnoid haemorrhage.

Controlled study of nimodipine in aneurysm patients treated early after subarachnoid hemorrhage.

We enrolled 75 consecutive patients admitted with subarachnoid hemorrhages in a randomized, double-blind, placebo-controlled trial to determine the effect of early intervention with nimodipine on outcome and cerebral blood flow. The cardioprotective effect of nimodipine was assessed by measuring the electrocardiographic changes over the first 3 days of drug treatment. There was a mild lowering of the mean cerebral blood flow in the nimodipine-treated group over the 21-day period. Analysis of the continuous electrocardiographic traces showed no difference between the nimodipine and placebo groups in the frequency or type of abnormality detected. At 3 months, 4 of the 38 patients receiving nimodipine had died, compared with 10 of the 37 placebo-receiving patients. Of the 50 eligible patients who had a proven cerebral aneurysm, 1 patient (4%) on nimodipine died compared with 6 (24%) receiving placebo (0.01 less than P less than 0.05, chi 2 test; approximate 95% confidence interval for mortality difference, 0.4% to 39.6%). We conclude that nimodipine does not increase the cerebral blood flow or protect the heart after a subarachnoid hemorrhage. There were no side effects from nimodipine. The trend toward improved outcome should be verified in a larger series of patients.

Early intervention with nimodipine in subarachnoid haemorrhage.

Seventy-five consecutive patients with subarachnoid haemorrhage (SAH) were entered into a randomized, double-blind, placebo-controlled trial prior to angiography in order to determine the effect of early intervention with nimodipine on blood pressure (BP), cerebral blood flow (CBF), and clinical outcome. Of these patients, 50 fulfilled the criteria for the final analysis (i.e. SAH due to cerebral aneurysm and receiving 21 days of treatment). There was no difference between the BP recordings of the two treatment groups, but mean CBF decreased slightly in the nimodipine group over the 21-day treatment period. At three months, one patient on nimodipine and six patients receiving placebo had died (P = 0.049, Fisher's exact test), but no significant difference was observed between the two groups, when the 'intent to treat' group of 75 patients was considered. We conclude that nimodipine does not increase CBF or alter BP following SAH, but an improved clinical outcome is evident at three months for patients with SAH due to cerebral aneurysm who had been treated with nimodipine. There were no side-effects due to nimodipine.

A clinicopathological study of patients following a subarachnoid hemorrhage.

The hypothalamus and myocardium of 54 patients (27 males and 27 females, age range 12 to 73 years) who died after subarachnoid hemorrhage (SAH) were examined histologically. In 42 patients, hypothalamic and myocardial lesions were found; in seven, hypothalamic lesions only; and in five, no hypothalamic nor myocardial lesions. A similar examination was performed on a control group of 25 patients (12 males and 13 females, age range 17 to 70 years) who had died from a variety of causes, all producing raised intracranial pressure. In these, no lesions were found in either the hypothalamus or the myocardium. The age of the patient, the site of the vascular pathology, and whether an operation was performed appeared to have no effect on the occurrence of hypothalamic and heart lesions; however, there was a correlation between these lesions, progressive neurological deterioration, and varying pulse rates and blood pressures. This study produces further evidence of the involvement of the autonomic nervous system in some of the deleterious effects of SAH, and a suggestion is made as to possible treatment.

Hypothalamic and myocardial lesions after subarachnoid haemorrhage.

The hypothalamus and myocardium of 12 patients who had died after a subarachnoid haemorrhage, and of six patients who had died from other intracranial pathology were examined. Only in the patients who had died from subarachnoid haemorrhage were histological lesions found in both the hypothalamus and myocardium. The possible significance of these findings is discussed with particular reference to the sympathetic nervous system.